Zhao Na, Li Siyu, Wu Hao, Wei Dong, Pu Ning, Wang Kexin, Liu Yashuang, Tao Ye, Song Zongming
Henan Eye Institute, Henan Eye Hospital, People's Hospital of Zhengzhou University, Henan University School of Medicine, Henan Provincial People's Hospital, Zhengzhou 450003, China.
College of Medicine, Zhengzhou University, Zhengzhou 450001, China.
Biomedicines. 2025 Apr 17;13(4):986. doi: 10.3390/biomedicines13040986.
Iron homeostasis plays an important role in maintaining cellular homeostasis; however, excessive iron can promote the production of reactive oxygen species (ROS). Ferroptosis is iron-dependent programmed cell death that is characterized by excessive iron accumulation, elevated lipid peroxides, and the overproduction of ROS. The maintenance of iron homeostasis is contingent upon the activity of the transferrin receptor (TfR), ferritin (Ft), and ferroportin (FPn). In the retina, iron accumulation and lipid peroxidation can contribute to the development of age-related macular degeneration (AMD). This phenomenon can be explained by the occurrence of the Fenton reaction, in which the interaction between divalent iron and hydrogen peroxide leads to the generation of highly reactive hydroxyl radicals. The hydroxyl radicals exhibit a propensity to attack proteins, lipids, nucleic acids, and carbohydrates, thereby instigating oxidative damage and promoting lipid peroxidation. Ultimately, these processes culminate in cell death and retinal degeneration. In this context, a comprehensive understanding of the exact mechanisms underlying ferroptosis may hold significant importance for developing therapeutic interventions. This review summarizes recent findings on iron metabolism, cellular ferroptosis, and lipid metabolism in the aging retina. We also introduce developments in the therapeutic strategies using iron chelating agents. Further refinements of these knowledges would deepen our comprehension of the pathophysiology of AMD and advance the clinical management of degenerative retinopathy. A comprehensive search strategy was employed to identify relevant studies on the role of ferroptosis in AMD. We performed systematic searches of the PubMed and Web of Science electronic databases from inception to the current date. The keywords used in the search included "ferroptosis", "AMD", "age-related macular degeneration", "iron metabolism", "oxidative stress", and "ferroptosis pathways". Peer-reviewed articles, including original research, reviews, meta-analyses, and clinical studies, were included in this paper, with a focus on the molecular mechanisms of ferroptosis in AMDs. Studies not directly related to ferroptosis, iron metabolism, or oxidative stress in the context of AMD were excluded. Furthermore, articles that lacked sufficient data or were not peer-reviewed (e.g., conference abstracts, editorials, or opinion pieces) were not considered.
铁稳态在维持细胞内环境稳定中起着重要作用；然而，过量的铁会促进活性氧（ROS）的产生。铁死亡是一种铁依赖性程序性细胞死亡，其特征是铁过度积累、脂质过氧化物升高以及ROS过度产生。铁稳态的维持取决于转铁蛋白受体（TfR）、铁蛋白（Ft）和铁转运蛋白（FPn）的活性。在视网膜中，铁积累和脂质过氧化可导致年龄相关性黄斑变性（AMD）的发生。这种现象可以通过芬顿反应来解释，即二价铁与过氧化氢之间的相互作用导致产生高活性的羟基自由基。羟基自由基倾向于攻击蛋白质、脂质、核酸和碳水化合物，从而引发氧化损伤并促进脂质过氧化。最终，这些过程导致细胞死亡和视网膜变性。在这种情况下，全面了解铁死亡的确切机制可能对开发治疗干预措施具有重要意义。本综述总结了衰老视网膜中铁代谢、细胞铁死亡和脂质代谢的最新研究结果。我们还介绍了使用铁螯合剂的治疗策略的进展。对这些知识的进一步完善将加深我们对AMD病理生理学的理解，并推动退行性视网膜病变的临床管理。我们采用了全面的检索策略来识别关于铁死亡在AMD中作用的相关研究。我们对PubMed和Web of Science电子数据库从创建到当前日期进行了系统检索。检索中使用的关键词包括“铁死亡”、“AMD”、“年龄相关性黄斑变性”、“铁代谢”、“氧化应激”和“铁死亡途径”。本文纳入了同行评审的文章，包括原创研究、综述、荟萃分析和临床研究，重点关注AMD中铁死亡的分子机制。与AMD背景下铁死亡、铁代谢或氧化应激不直接相关的研究被排除。此外，缺乏足够数据或未经同行评审的文章（如会议摘要、社论或观点文章）未被考虑。
